Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen

Masasuke Ohno, Atsushi Natsume, Ken Ichiro Iwami, Hidetaka Iwamizu, Kana Noritake, Daiki Ito, Yuki Toi, Motokazu Ito, Kazuya Motomura, Jun Yoshida, Kazuhiro Yoshikawa, Toshihiko Wakabayashi
Cancer Science 2010, 101 (12): 2518-24
The isotype of epidermal growth factor receptor variant III (EGFRvIII) is often identified in glioblastomas. Previously, we created a mouse monoclonal antibody, 3C10 (IgG2b), that specifically recognized EGFRvIII, and a recombinant single-chain variable fragment of 3C10. The aim of the current study was to develop genetically engineered T cells, termed T-bodies, that express a chimeric receptor consisting of the 3C10 single-chain variable fragment coupled to signaling modules such as the CD3zeta (ζ) chain, for the treatment of tumors expressing mutant EGFR. After successful construction of the chimeric 3C10/CD3ζ T-cell receptor, its expression on the T-body was observed using western blotting and flow cytometry. The specificity of the T-body for EGFRvIII was evaluated using an interferon-gamma Elispot assay and a standard (51) Cr-release cytotoxicity assay. Furthermore, we demonstrated that the systemically delivered T-body infiltrated the intrabrain tumor and significantly delayed tumor growth. These results indicate that the T-body expressing the chimeric 3C10/CD3ζ T-cell receptor specifically recognized glioma cells expressing EGFRvIII. In conclusion, T-body-based immunotherapy appears to be a promising approach for the treatment of glioma.

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